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DOI: 10.1055/s-0029-1218636
A Concise Synthesis of (S)-2-(Fluorodiphenylmethyl)pyrrolidine: A Novel Organocatalyst for the Stereoselective Epoxidation of α,β-Unsaturated Aldehydes
Publikationsverlauf
Publikationsdatum:
08. Januar 2010 (online)
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Abstract
A concise synthesis of (S)-2-(fluorodiphenylmethyl)pyrrolidine from cheap, commercially available starting materials is described. Pertinent features of this synthetic route include ease of synthesis, facile purification steps, and an operationally simple deoxyfluorination step to install the C-F bond.
Key words
diethylaminosulfur trifluoride - fluorination - organocatalyst - proline - synthesis
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References
(S)-2-(Fluorodiphenylmethyl)pyrrolidine (1) (98% ee HPLC, 97%) (500 mg = 348.50 CHF) and its R-enantiomer (500 mg = 332.16 CHF) are available from Sigma-Aldrich.
9For this analysis (R)-7 was prepared from d-proline following the procedure described in this manuscript. HPLC: Derivatisation with Ac2O (1.2 equiv) and DMAP (1.2 equiv) in CH2Cl2 at r.t. for 2 h. Removal of the solvent and purification by flash column chromatography (SiO2, EtOAc). HPLC on a Reprosil Chiral-OM, 5 µm column (1.0 mL/min, i-PrOH-n-hexane, 1:6): (S)-7 t R = 6.56 min and (R)-7 t R = 6.21 min.
12Whilst the product is identical to known material,6 the yellow colouration may be removed by the following simple procedure to yield a clear, colourless oil: To the yellow oil (100 mg) was added HCl in MeOH (500 µL, 1.25 mol/L). The resulting suspension was filtered and the solid was washed with Et2O. The solid was dissolved in a mixture of EtOAc (5.0 mL) and NaOH (5.0 mL, 2.0 mol/L, pH >9). The layers were separated, the organic phase was washed with brine (5.0 mL), dried (Na2SO4) and concentrated in vacuo to give a colourless oil (98.5 mg).
13Sigma Aldrich Specification Sheet (Product Number 552569, CAS Number 274674-23-6).